Efficacy and safety of single-pill amlodipine/losartan versus losartan in patients with inadequately controlled hypertension after losartan treatment: a multicenter, double-blind, randomized phase III clinical trial.

Objective: Single-pill amlodipine besylate (AML) plus losartan (LOS) has been used to treat inadequately controlled hypertension after antihypertensive monotherapy; however, relevant data in China are limited. This study aimed to compare the efficacy and safety of single-pill AML/LOS and LOS alone in Chinese patients with inadequately controlled hypertension after LOS treatment. Methods: In this multicenter, double-blind, randomized, controlled phase III clinical trial, patients with inadequately controlled hypertension after 4 weeks of LOS treatment were randomized to receive daily single-pill AML/LOS (5/100 mg, AML/LOS group, N = 154) or LOS (100 mg, LOS group, N = 153) tablets for 8 weeks. At weeks 4 and 8 of treatment, sitting diastolic and systolic blood pressure (sitDBP and sitSBP, respectively) and the BP target achievement rate were assessed. Results: At week 8, the sitDBP change from baseline was greater in the AML/LOS group than in the LOS group (-8.84 ± 6.86 vs. -2.65 ± 7.62 mmHg, P < 0.001). In addition, the AML/LOS group also showed greater sitDBP change from baseline to week 4 (-8.77 ± 6.60 vs. -2.99 ± 7.05 mmHg) and sitSBP change from baseline to week 4 (-12.54 ± 11.65 vs. -2.36 ± 10.33 mmHg) and 8 (-13.93 ± 10.90 vs. -2.38 ± 12.71 mmHg) (all P < 0.001). Moreover, the BP target achievement rates at weeks 4 (57.1% vs. 25.3%, P < 0.001) and 8 (58.4% vs. 28.1%, P < 0.001) were higher in the AML/LOS group than those in the LOS group. Both treatments were safe and tolerable. Conclusion: Single-pill AML/LOS is superior to LOS monotherapy for controlling BP and is safe and well tolerated in Chinese patients with inadequately controlled hypertension after LOS treatment.

Shudi Erzi San relieves ovary aging in laying hens.

Poultry meat and eggs are a primary source of animal protein. To meet the market needs, high yield laying hens are reared continuously, resulting in quick ovary aging. Thus, we investigated the anti-aging effects of Shudi Erzi San (SES) on laying hens. Sixty 300-day-old laying hens were divided into 2 experimental groups and a control group. The control group was fed on a basic diet, which was supplemented with 1% and 2% SES for experimental groups I and II, respectively. Egg quality and changes in serum hormones and blood-biochemical indicators of laying hens were determined. The rate of egg production was significantly higher in group Ⅱ than in both the control and group Ⅰ by 9.29 and 8.22 percentage points, respectively (P < 0.05). Eggshell strength of groups Ⅰ and Ⅱ were significantly higher than that of the control group (P < 0.01). Albumen height and Haugh Units of group Ⅱ were significantly higher than those of the control (P < 0.05). Serum levels of follicle stimulating hormone and estradiol in group Ⅱ were significantly higher than those of both the control and group Ⅰ (P < 0.05), whereas groups Ⅰ and Ⅱ had significantly higher serum levels of luteinizing hormone than the control (P < 0.05). Levels of superoxide dismutase (SOD) did not significantly differ between the control and group Ⅰ (P > 0.05), but SOD and malondialdehyde (MDA) levels in group Ⅱ were significantly higher and lower, respectively (P < 0.05) when compared to the control. Compared with the control, uric acid levels in groups Ⅰ and Ⅱ were significantly lower (P < 0.05), as was urea nitrogen in group Ⅱ (P < 0.05). Transcriptome and KEGG pathway analysis of ovarian tissues of laying hens showed a significant immune related signal pathway as the possible main regulator of a lysosome related signal pathway. Thus, supplementing chicken feed with SES improves egg production and quality and alleviates ovarian decline in laying hens.

Low level of mancozeb exposure affects ovary in mice.

Mancozeb (MCZ) is widely used as a protective fungicide. This study aimed to explore the effects of low level MCZ exposure on ovary in mice. Twenty Kunming mice were randomly divided into control and MCZ groups (10 mice each). The mice in the MCZ group were given 100 mg/kg MCZ daily via gavage. The mice were sacrificed to collect serum and ovaries on day 31. The experimental indicators were then assessed. The weight of MCZ-exposed mice significantly reduced while ovarian index significantly increased compared with the control group. The FSH, LH, E2, P, CAT, SOD and MDA contents in the serum were significantly decreased and the content of estradiol significantly increased after MCZ exposure. Histological observation showed that the ovarian structure of mice exposed to MCZ was damaged, and the apoptosis was increased. Immunohistochemistry and RT-qPCR showed that the expression of Bax, caspase-3 and caspase-9 significantly increased in the MCZ- group. Conversely, Bcl-2 expression significantly decreased. Transcriptome sequencing showed that the expression of NADH dehydrogenase ND3, ND4L, ND6 subunits, Cyt b, and SDHC genes in mitochondria were down-regulated after MCZ exposure, similar to real-time PCR analysis. These results collectively indicate that the MCZ can affect the abnormal function of mitochondrial respiratory chain, lead to oxidative phosphorylation decoupling, produce oxidative stress, and finally cause ovarian injury and apoptosis in mice.

Microstructures and Tensile Properties of 9Cr-F/M Steel at Elevated Temperatures.

Tensile properties and microstructure changes under different stress states of tempered 9Cr-F/M steel were characterized using a transmission electron microscope (TEM), electron backscatter diffraction (EBSD), scanning electron microscopy (SEM), Vickers hardness tester, and tensile tester. This tempered steel has a typical lath martensite structure with only a few polygonal ferrites embedded, and M23C6 and MX phases nucleated on the lath boundaries or within the sub-grains. At elevated temperatures, the strength of the steel decreases. However, the elongation at 400 °C is lower than that at room temperature. For the necking zone, tensile deformation made the grain elongated to the direction of applied stress and thus the grain's cross-section becomes smaller. For samples with rectangular working area cross-section, the deformation in the TD direction was more severe than that in the ND direction, which made the grain elongated in the TD direction. These results can provide some guidance for composition optimization of the 9Cr-F/M steel and facilitate a better understanding of the fracture mechanism under different stress states.

Li2ZrO3-Coated Monocrystalline LiAl0.06Mn1.94O4 Particles as Cathode Materials for Lithium-Ion Batteries.

Li2ZrO3-coated and Al-doped micro-sized monocrystalline LiMn2O4 powder is synthesized through solid-state reaction, and the electrochemical performance is investigated as cathode materials for lithium-ion batteries. It is found that Li2ZrO3-coated LiAl0.06Mn1.94O4 delivers a discharge capacity of 110.90 mAhg-1 with 94% capacity retention after 200 cycles at room temperature and a discharge capacity of 104.4 mAhg-1 with a capacity retention of 87.8% after 100 cycles at 55 °C. Moreover, Li2ZrO3-coated LiAl0.06Mn1.94O4 could retain 87.5% of its initial capacity at 5C rate. This superior cycling and rate performance can be greatly contributed to the synergistic effect of Al-doping and Li2ZrO3-coating.

Therapeutic effect of Schisandrin A on avian colibacillosis through gut-liver axis.

This study evaluated the therapeutic efficacy of Schisandrin A on systemic colibacillosis of chickens. One hundred and eighty, 1-day-old Hailan Brown chickens were divided into 6 groups of 30 chickens each and assigned to the following treatments: 1) uninfected/untreated control; 2) infected Escherichia coli; 3) infected-plus low dose of Schisandrin A therapy (50 mg/kg); 4) infected-plus medium dose of Schisandrin A therapy (100 mg/kg); 5) infected-plus high dose of Schisandrin A therapy (200 mg/kg) and 6) infected-plus antimicrobial therapy (florfenicol). Each group of chickens was placed in cages with a photoperiod of 12 h of light and 12 h of dark. Feed and water for all groups were provided ad libitum for the duration of the study. On d 14, all the chickens except the uninfected control group were intraperitoneally inoculated with a fresh culture of E. coli containing 1 × 108 CFU/mL. The parameters measured included: average daily weight gain (ADG), percent survivability, liver index, serum activity of enzymes (ALT and AST), hepatic and intestinal concentrations of TNF-α, IL-1ß, IL-6, IL-8, and LPS, expression of tight junction proteins (occludin, ZO-1, and claudin-1), relative abundance of bacterial species and histopathological changes in hepatic and intestinal tissue. The results showed that the medium and high doses of Schisandrin A ameliorated the detrimental effects of colibacillosis on weight gain. Regarding organ indexes, E. coli infection induced a significant increase in liver index, all the doses of Schisandrin A produced a significant reduction of liver index in comparison to the E. coli infected control. Serum activity of ALT and AST enzymes significantly increased due to E. coli infection, with the exception of the low dose of Schisandrin A for AST enzyme activity, all the Schisandrin A treatments significantly lowered enzyme activity in comparison to the E. coli infected control. Regarding concentrations of inflammatory markers in hepatic and intestinal, E. coli infection caused a significant increase in TNF-α, IL-1ß, IL-6, and IL-8, except the lowest dose of Schisandrin A for IL-1ß, the rest of the doses tested were able to significantly reduced the concentrations of inflammatory markers. Concentrations of LPS in hepatic and intestinal tissues were significantly increased by E. coli infection, all doses of Schisandrin A significantly reduced the concentration of LPS in hepatic and intestinal tissue. E. coli infection significantly reduced the expression of 2 tight junction proteins (ZO-1 and Claudin-1), the higher doses of Schisandrin A were effective in significantly increasing the expression of these tight junction proteins when compared with the E. coli infected control. Taken together, these results show that Schisandrin A has potential as an alternative therapy for the treatment of colibacillosis in chickens.

Perfluorooctanoic acid exposure in early pregnancy induces oxidative stress in mice uterus and liver.

This study aimed to explore the mechanism of perfluorooctanoic acid (PFOA) toxicity on the uterus and liver of mice during early pregnancy. Pregnant mice were given 0, 1, 5, 10, 20, and 40 mg/kg PFOA daily by gavage from gestational day (GD) 1-7 and sacrificed on GD 9. Subsequently, several toxicity parameters were evaluated, including the uterus and liver weights, liver and uterine indexes, histopathological changes of the liver and uterus, and levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the liver. We also determined the expressions of FAS, FASL, Bax, Bcl-2, and Caspase-3 in decidual cells by immunohistochemistry and the TUNEL assay to detect apoptosis uterine cells. The results showed that PFOA increased the liver weights and reduced the uterus index in a dose-dependent manner. With increasing doses of PFOA, the levels of SOD and GSH-Px were significantly decreased, and MDA increased substantially in liver tissue. 20 mg/kg and 40 mg/kg of PFOA caused more substantial harm to the uterus, thus a higher probability for congestion and resorption. The expression of FAS, FASL, Bax, and Caspase-3 in decidual cells of the uterus in the PFOA treatment groups significantly increased in a dose-dependent manner. The expression of Bcl-2 was downregulated, decreasing the Bcl-2/Bax ratio. At gestation day 9, the control group had significantly fewer apoptotic cells in the uterus and shallower staining than the 40 mg/kg PFOA group. The findings of this study suggest that oxidative damage may be one of the mechanisms by which PFOA induces liver toxicity, and a subsequent increase in uterine cell apoptosis may cause embryo loss or damage.

A Polymer-in-Salt Electrolyte with Enhanced Oxidative Stability for Lithium Metal Polymer Batteries.

The lithium (Li) metal polymer battery (LMPB) is a promising candidate for solid-state batteries with high safety. However, high voltage stability of such a battery has been hindered by the use of polyethylene oxide (PEO), which oxidizes at a potential lower than 4 V versus Li. Herein, we adopt the polymer-in-salt electrolyte (PISE) strategy to circumvent the disadvantage of the PEO-lithium bis(fluorosulfonyl)imide (LiFSI) system with EO/Li ≤ 8 through a dry ball-milling process to avoid the contamination of the residual solvent. The obtained solid-state PISEs exhibit distinctly different morphologies and coordination structures which lead to significant improvement in oxidative stability. P(EO)1LiFSI has a low melting temperature, a high ionic conductivity at 60 °C, and an oxidative stability of ∼4.5 V versus Li/Li+. With an effective interphase rich in inorganic species and a good stability of the hybrid polymer electrolyte toward Li metal, the LMPB constructed with Li||LiNi1/3Co1/3Mn1/3O2 can retain 74.4% of capacity after 186 cycles at 60 °C under the cutoff charge voltage of 4.3 V. The findings offer a promising pathway toward high-voltage stable polymer electrolytes for high-energy-density and safe LMPBs.

Effects of maternal exposure to PFOA on testes of male offspring mice.

This study was conducted to explore the effects of maternal exposure to perfluorooctanoic acid (PFOA) on testicular development of male offspring mice. 20 pregnant Kunming mice were randomly divided into control group and PFOA exposure group with 10 mice of each. In PFOA exposure group, pregnant mice were given 5 mg/kg BW PFOA daily by gavage during gestation. Male offspring mice were killed to separate serum and collect testis at postpartum day 21, then tested the experimental indicators. The results showed that compared with control group, the content of PFOA in the serum of PFOA-exposed mice increased significantly and testosterone content is significantly reduced. Histological observations revealed architectural damages in testis in PFOA exposed groups and the apoptosis was increased. Transcriptome sequencing results showed that the U4/U6 snRNA coding genes snu13 and prp19 complex coding genes HSP73 were up-regulated and the U5 snRNA coding genes Brr2, Prp8 and EJC/TREX coding THOC genes were down-regulated after PFOA exposure Real-time PCR confirmed this result. These results indicate that the exposure of pregnant mice to perfluorooctanoic acid will have a damaging effect on the development of testes in male offspring mice, which may be due to blocked activation of the shear body, changes in structural functions, and inability to perform shear functions.

UCPs/Zn2GeO4:Mn2+/g-C3N4 heterojunction engineered injectable thermosensitive hydrogel for oxygen independent breast cancer neoadjuvant photodynamic therapy.

Neoadjuvant chemotherapy for the treatment of breast cancer can provide the option of surgery for patients with a large tumor mass or increase the rate of breast conservation. However, some patients are not sensitive to chemotherapeutic drugs, and therefore this may cause them to miss their optimal chance for surgery. Herein, photodynamic therapy (PDT) was chosen instead of chemotherapy as a neoadjuvant treatment for breast cancer because of its effectiveness against different cancer cells and the lack of side effects in normal tissues. Considering the hypoxic environment of tumors and the tissue penetration depth, a heterojunction Zn2GeO4:Mn2+/g-C3N4 was designed and combined with upconversion materials NaYF4:Yb3+, Tm3+ and hyaluronic acid to form a NaYF4:Yb3+, Tm3+/Zn2GeO4:Mn2+/g-C3N4@HA (UZC@HA) photosensitizer. After intratumoral administration using a thermosensitive hydrogel as a carrier, under a 980 nm laser, UZC@HA can generate holes and electrons to oxidize water to form a hydroxyl radical (˙OH) and react with O2 to produce the superoxide ion (˙O2-), respectively. The thermosensitive hydrogel not only supplies water, but also ensures the high loading capacity of UZC@HA. HA on the UZC can bind specifically with CD44R-overexpressing tumor cells and help the photosensitizer to target tumor sites. Thus, near infrared (NIR) mediated oxygen-independent PDT can be realized. After 12 d of treatment, the tumor mass was significantly reduced and no side effects in normal tissues were observed. Our work shows the potential of the NIR mediated heterojunction UZC@HA to act as a photosensitizer for neoadjuvant PDT in breast cancer and may open a new avenue for exploration of PDT and provide more options for breast cancer patients.

Thickness-Dependent Beneficial Effect of the ZnO Layer on Tailoring the Li/Li7La3Zr2O12 Interface.

Li7La3Zr2O12 (LLZO)-based ceramics are well-known as the most promising solid electrolytes for all-solid-state lithium metal batteries. However, its practical application has been significantly hindered by high Li/LLZO interfacial impedance as a result of poor interfacial contact. To solve these issues, in this work, the ZnO layer was magnetron sputter-deposited on Li6.55La2.95Ca0.05Zr1.5Ta0.5O12 (LLCZTO) pellets. It was found that by introducing a 200 nm thick ZnO layer, the interfacial area specific resistance was sharply reduced to as low as 1% that of pristine LLCZTO; meanwhile, Li plating/stripping performance was improved significantly with a long life span of 320 h and a low polarization potential of 0.1 V, whereas a thicker ZnO layer of 600 nm can only improve the interface contact to a very limited extent because of the accumulated volume expansion induced by the in situ transformation of ZnO to the Li-Zn alloy, demonstrating the thickness-dependent beneficial effect of the ZnO layer on improving the Li/LLCZTO interfacial contact and therefore reducing the interfacial resistance. Accordingly, the evolution of the interfacial contact mode and the Li+ migration mechanism during the Li plating/stripping process without or with ZnO layers of different thicknesses were discussed in detail.

Maternal exposure to perfluorooctanoic acid (PFOA) causes liver toxicity through PPAR-α pathway and lowered histone acetylation in female offspring mice.

The study was conducted to investigate the liver toxicity in female offspring mice induced by maternal exposure to perfluorooctanoic acid (PFOA). Fifty pregnant Kunming mice were randomly divided into 5 groups with 10 of each, which were treated with 0.2 mL PFOA solution dissolved with deionized water at 0, 1, 2.5, 5, and 10 mg/kg BW, respectively, from the pregnancy day (PND) 0 to day 17. Female offspring mice were sacrificed to collect serum and liver at postpartum day 21. The results showed that PFOA significantly reduced the body weight at weaning and the survival rate of the female offspring mice (P < 0.01) increased the liver index of the pups (P < 0.01). Meanwhile, PFOA also caused hepatic bleeding, local necrosis, and enlargement of hepatocytes and vacuolization. The levels of serum AST, ALT, SOD, and CAT in PFOA treatment group were upregulated significantly (P < 0.01). The expressions of Acot1, Acox1, and Acsl1 genes were increased significantly (P < 0.01). The expression of PPAR-α gene was decreased significantly (P < 0.01). There was no significant difference in the expression of Cpt1a gene among the 5 groups. HAT activity was reduced significantly and HDAC activity was increased significantly. The expression of anti-acetyl-histone H3 and acetyl-histone H4 was reduced significantly. Thus, our findings indicate that exposure to PFOA during pregnancy affects the growth and development of the pups and causes liver damage, disrupting the secretion of enzymes involved in fatty acid oxidation induced by PPAR-α, leading to liver oxidative stress and a decrease in the degree of histone acetylation. Elevated HDAC may aggravate downstream fatty acid metabolism disorders through PPAR-α.

Nb-doped and Al2O3 + B2O3-coated granular secondary LiMn2O4 particles as cathode materials for lithium-ion batteries.

In this work, to improve the cyclability and high-temperature performance of cubic spinel LiMn2O4 (LMO) as cathode materials, Nb5+-doped LiMn2O4 powders coated and uncoated with Al2O3 and/or B2O3 were synthesized via the modified solid-state reaction method. It was found that Nb5+-doped and B2O3 + Al2O3-coated LMO powders comprising 5 µm granular agglomerated fine primary particles smaller than 350 nm in diameter exhibited superior electrochemical properties with initial discharge capacity of 101.68 mA h g-1; we also observed capacity retention of 96.31% after 300 cycles at room temperature (RT) and that of 98% after 50 cycles at 55 °C and 1C rate.

Lithium Difluorophosphate as a Dendrite-Suppressing Additive for Lithium Metal Batteries.

The notorious lithium (Li) dendrites and the low Coulombic efficiency (CE) of Li anode are two major obstacles to the practical utilization of Li metal batteries (LMBs). Introducing a dendrite-suppressing additive into nonaqueous electrolytes is one of the facile and effective solutions to promote the commercialization of LMBs. Herein, Li difluorophosphate (LiPO2F2, LiDFP) is used as an electrolyte additive to inhibit Li dendrite growth by forming a vigorous and stable solid electrolyte interphase film on metallic Li anode. Moreover, the Li CE can be largely improved from 84.6% of the conventional LiPF6-based electrolyte to 95.2% by the addition of an optimal concentration of LiDFP at 0.15 M. The optimal LiDFP-containing electrolyte can allow the Li||Li symmetric cells to cycle stably for more than 500 and 200 h at 0.5 and 1.0 mA cm-2, respectively, much longer than the control electrolyte without LiDFP additive. Meanwhile, this LiDFP-containing electrolyte also plays an important role in enhancing the cycling stability of the Li||LiNi1/3Co1/3Mn1/3O2 cells with a moderately high mass loading of 9.7 mg cm-2. These results demonstrate that LiDFP has extensive application prospects as a dendrite-suppressing additive in advanced LMBs.

Investigation of Interference Models for RFID Systems.

The reader-to-reader collision in an RFID system is a challenging problem for communications technology. In order to model the interference between RFID readers, different interference models have been proposed, mainly based on two approaches: single and additive interference. The former only considers the interference from one reader within a certain range, whereas the latter takes into account the sum of all of the simultaneous interferences in order to emulate a more realistic behavior. Although the difference between the two approaches has been theoretically analyzed in previous research, their effects on the estimated performance of the reader-to-reader anti-collision protocols have not yet been investigated. In this paper, the influence of the interference model on the anti-collision protocols is studied by simulating a representative state-of-the-art protocol. The results presented in this paper highlight that the use of additive models, although more computationally intensive, is mandatory to improve the performance of anti-collision protocols.

Rosuvastatin reduces ischemia-reperfusion injury in patients with acute coronary syndrome treated with percutaneous coronary intervention.

BACKGROUND: Statins reduce the incidence of cardiovascular events after percutaneous coronary intervention (PCI), but no clinical studies have investigated the role of statins in ischemia-reperfusion injury after PCI. HYPOTHESIS: Rosuvastatin could reduce ischemia-reperfusion injury in patients with acute coronary syndrome treated with PCI. OBJECTIVES: We investigated the effects of rosuvastatin on ischemia-reperfusion injury in patients with acute coronary syndrome after PCI and evaluated short-term prognosis. METHODS: Patients scheduled for emergent PCI were given either rosuvastatin for ≥6 months (10 mg/d, every night; n = 55) or no statins (control group; n = 65). Serum superoxide dismutase activity, malondialdehyde, brain natriuretic peptide (BNP), and high-sensitivity C-reactive protein (hs-CRP) were determined before and after PCI, as well as left ventricular ejection fraction and left ventricular end-diastolic volume. Major adverse cardiac events were observed at follow-ups for 6 months. RESULTS: Superoxide dismutase activity in the rosuvastatin-treated group was higher than that of the control group; serum levels of malondialdehyde were lower. BNP and hs-CRP levels in the rosuvastatin-treated group were lower than that of the control group. Four weeks after PCI, the left ventricular ejection fraction in the treatment group was higher than that of the control group, and the left ventricular end-diastolic volume was lower. At the 6-month follow-up, there was no difference in major adverse cardiac events between the 2 groups. CONCLUSIONS: Rosuvastatin before PCI reduced ischemia-reperfusion injury in patients with acute coronary syndrome, which suggests the importance of application of rosuvastatin before PCI for early intervention.

[Expression of Bcl-2 and Bax in the impairment of contralateral testes of unilateral cryptorchidism in rats].

OBJECTIVE: To investigate the relationship between germ cell apoptosis and expressions of Bcl-2 and Bax in contralateral testes of experimental unilateral cryptorchid rats. METHODS: Twenty male Sprague-Dawley rats were randomly divided into 2 groups (namely cryptorchid group and control group), with 10 rats in each group. Cryptorchid animal model was established, and contralateral testes were captured 90 days later. The evidence of germ cell apoptosis was detected by TUNEL assay. The expressions of Bcl-2 and Bax were detected by immunohistochemical method. RESULTS: In the contralateral testes of experimental unilateral cryptorchidism, apoptosis index of germ cell and Bax expression significantly increased compared with those in the control group, respectively (P < 0.01), while Bcl-2 expression and testis weight obviously decreased (P <0.01). The apoptotic cells were mostly pachytene spermatocytes and round spermatids. CONCLUSION: The germ cell apoptosis is highly correlated with expressions of Bcl-2 and Bax in contralateral testes of experimental unilateral cryptorchidism. Bcl-2/Bax plays an important role in germ cell apoptosis.